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The inter-particle interference of lignocellulosic materials describes the order of the macromolecules at a larger size scale, which can give information about the pore structure, and interface of cellulose and lignin. The pore structure and interface influence the rate of enzymatic hydrolysis and thermal decomposition in cellulosic ethanol manufacturing. In this study, the inter-particle interference of cellulose and lignin of three major categories of lignocellulosic materials: wood-based (cedar and oak), energy crop (bamboo), and agricultural or forestry waste (palm) were evaluated. Scanning electron microscopy (SEM) reveals morphological irregularities in the case of bamboo and palm, which may form nucleation sites for faster accessibility to enzyme molecules. Small-angle X-ray scattering (SAXS) shows increased power-law exponent for palm, suggesting a less clustered structure, which was consistent with the rough surface morphology as detected by the SEM. Differential Scanning Calorimetry (DSC) showed a higher temperature maximum for cedar and oak, which is indicative of higher intermolecular forces within their organic compounds, and could result in slower disintegration of the macromolecules during biochemical processing. This study will help to estimate the activity of the macromolecules and absorption capacity of lignocellulosic materials during biochemical processing., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The study of lignocellulosic materials calls for understanding the structure, and function of different cellulosic materials from diverse sources to scale-up cellulosic ethanol production. For the first time, a systematic assessment of the molecular and supramolecular structure highlighting the similarities and dissimilarities of three major categories of lignocellulosic materials: wood-based (cedar and oak), energy crop (bamboo), and agricultural or forestry waste (palm) are reported. The cellulose, hemicellulose, and lignin constituents were compared for their suitability in cellulosic ethanol production. FTIR showed structural variations within the functional groups with notable OH group in the palm and CC group in cedar. From the X-ray scattering, bamboo exhibited the highest crystallinity (49.5%), and palm showed the lowest crystallinity (22.6%) and crystallite size (2.6 nm). TGA revealed high cellulose amount and stable structure for cedar and oak, and the most unstable structure in the palm, which indicates a better cellulose/hemicellulose accessibility and biodegradability for enzymatic or chemical action in the palm. This comparative assessment can greatly facilitate material selection and component mixture, for developing an efficient and cost-effective biochemical process in ethanol manufacturing., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Zika virus infection during pregnancy can cause congenital brain and eye abnormalities and is associated with neurodevelopmental abnormalities (1-3). In areas of the United States that experienced local Zika virus transmission, the prevalence of birth defects potentially related to Zika virus infection during pregnancy increased in the second half of 2016 compared with the first half (4). To update the previous report, CDC analyzed population-based surveillance data from 22 states and territories to estimate the prevalence of birth defects potentially related to Zika virus infection, regardless of laboratory evidence of or exposure to Zika virus, among pregnancies completed during January 1, 2016-June 30, 2017. Jurisdictions were categorized as those 1) with widespread local transmission of Zika virus; 2) with limited local transmission of Zika virus; and 3) without local transmission of Zika virus. Among 2,004,630 live births, 3,359 infants and fetuses with birth defects potentially related to Zika virus infection during pregnancy were identified (1.7 per 1,000 live births, 95% confidence interval [CI] = 1.6-1.7). In areas with widespread local Zika virus transmission, the prevalence of birth defects potentially related to Zika virus infection during pregnancy was significantly higher during the quarters comprising July 2016-March 2017 (July-September 2016 = 3.0; October-December 2016 = 4.0; and January-March 2017 = 5.6 per 1,000 live births) compared with the reference period (January-March 2016) (1.3 per 1,000). These findings suggest a fourfold increase (prevalence ratio [PR] = 4.1, 95% CI = 2.1-8.4) in birth defects potentially related to Zika virus in widespread local transmission areas during January-March 2017 compared with that during January-March 2016, with the highest prevalence (7.0 per 1,000 live births) in February 2017. Population-based birth defects surveillance is critical for identifying infants and fetuses with birth defects potentially related to Zika virus regardless of whether Zika virus testing was conducted, especially given the high prevalence of asymptomatic disease. These data can be used to inform follow-up care and services as well as strengthen surveillance., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

A high-sensitivity benchtop x-ray fluorescence (XRF) imaging system, based on a high-power x-ray source and silicon drift detector, has been developed. This system allows gold L-shell XRF-based quantitative imaging of gold nanoparticles (GNPs) at concentrations as low as 0.007  mg/cm 3 (7 ppm) in biological tissues/water. Its capability for biomedical applications was demonstrated by imaging the GNP distribution within a small (∼12×11×2  mm 3 ) ex vivo sample (extracted from a murine tumor after intravenous GNP administration). The results suggest direct translatability for routine preclinical ex vivo imaging tasks involving GNPs, as well as the possibility for in vivo imaging of small/superficial animal tumors.

Lambert-Eaton Myasthenic Syndrome (LEMS) is an autoimmune-mediated neurological disorder that manifests as muscle fatigue, diminished tendon reflexes, with symptoms of cholinergic overactivity. It can be associated with certain neoplastic conditions, the most common being small cell lung carcinoma (SCLC). The basic pathophysiology involved is antibody-mediated targeting of voltage-gated calcium channels (VGCC), which decreases the release of acetylcholine in the synaptic junction. Multiple treatment options have been introduced in the past and, recently, a new drug, amifampridine, has been approved by the Food and Drug Administration (FDA) for the treatment of weakness associated with these patients. We summarize this newly introduced drug with a brief description of other treatment options available., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Anwar et al.)

The use of bone marrow mesenchymal stem cells (BMSCs) has great potential in cell therapy, particularly in the orthopedic field. BMSCs represent a valuable renewable cell source that have been successfully utilized to treat damaged skeletal tissue and bone defects. BMSCs can be induced to differentiate into osteogenic lineages via the addition of inducers to the growth medium. The present study examined the effects of all-trans retinoic acid (ATRA) and curcumin on the osteogenic differentiation of mouse BMSCs. Morphological changes, the expression levels of the bone-associated gene markers bone morphogenetic protein 2, runt-related transcription factor and osterix during differentiation, an in vitro mineralization assay, and changes in osteocalcin expression revealed that curcumin supplementation promoted the osteogenic differentiation of BMSCs. By contrast, the application of ATRA increased osteogenic differentiation during the early stages, but during the later stages, it decreased the mineralization of differentiated cells. In addition, to the best of our knowledge, the present study is the first to examine the effect of curcumin on the osteogenic potency of mouse embryonic fibroblasts (MEFs) after reprogramming with human lim mineralization protein (hLMP-3), which is a positive osteogenic regulator. The results revealed that curcumin-supplemented culture medium increased hLMP-3 osteogenic potency compared with that of MEFs cultured in the non-supplemented medium. The present results demonstrate that enrichment of the osteogenic culture medium with curcumin, a natural osteogenic inducer, increased the osteogenic differentiation capacity of BMSCs as well as that of MEFs reprogrammed with hLMP-3.

In this study, we developed a detector's eye view (DEV)-based ordered subsets expectation maximization (OSEM) algorithm for more accurate reconstruction of benchtop x-ray fluorescence computed tomography (XFCT) images. The proposed approach was tested using two sets of benchtop XFCT imaging data derived from a newly performed gold nanoparticle (GNP)-containing phantom imaging study and a previously published postmortem benchtop XFCT imaging study of a tumor-bearing mouse injected with GNPs. DEV-based OSEM resulted in higher spatial resolution (up to ~20% decrease in the full width at half maximum values of the regions of interest), compared with filtered back-projection (FBP) and traditional OSEM. It also resulted in up to an order of magnitude smaller background noise in the reconstructed images than FBP, while producing consistently less background noise than traditional OSEM.

The absence of proper nanoscale experimental techniques to investigate the dose-enhancing properties of gold nanoparticles (GNPs) interacting with radiation has prompted the development of various Monte Carlo (MC)-based nanodosimetry techniques that generally require considerable computational knowledge, time and specific tools/platforms. Thus, this study investigated a hybrid computational framework, based on the electron dose point kernel (DPK) method, by combining Geant4 MC simulations with an analytical approach. This hybrid framework was applied to estimate the dose distributions around GNPs due to the secondary electrons emitted from GNPs irradiated by various photon sources. Specifically, the equivalent path length approximation was used to rescale the homogeneous DPKs for heterogeneous GNPs embedded in water/tissue. Compared with Geant4 simulations, the hybrid framework halved calculation time while utilizing fewer computer resources, and also resulted in mean discrepancies less than 20 and 5% for Yb-169 and 6 MV photon irradiation, respectively. Its appropriateness and computational efficiency in handling more complex cases were also demonstrated using an example derived from a transmission electron microscopy image of a cancer cell containing internalized GNPs. Overall, the currently proposed hybrid computational framework can be a practical alternative to full-fledged MC simulations, benefiting a wide range of GNP- and radiation-related applications.

Herein, we have investigated the interaction of bovine serum albumin (BSA), the most abundant globular protein, with a conventional cationic surfactant, cetyldimethylethylammonium bromide (CDMEAB), through a conductivity technique in the absence/presence of electrolyte solutions at various temperatures (298.15-323.15 K). The interaction of the protein with drugs/surfactants and other additives plays a crucial role in the body. Hence, the main concern of the study is to extract the impact of BSA on surfactant molecules and vice versa . From the specific conductivity versus concentration of surfactant plots, three different noticeable critical micelle concentration ( c *) values were obtained for pure CDMEAB and its mixture with protein/protein + salts. The presence of BSA and electrolytes altered the c * values of CDMEAB revealing interactions among the studied constituents where the salt solutions reduced the c * values and created a convenient environment for favorable micellization. The negative magnitudes achieved for standard free energy changes (Δ G 0 m ) suggest spontaneity of micellization while the values of Δ H 0 m and Δ S 0 m signified the existence of some electrostatic and hydrophobic interactions. The values of molar heat capacity (Δ C 0 m ) were positive as well as small which was an indication of less structural deformation. Molecular Dynamics (MD) simulation for all atoms revealed that the salt ions promoted non-covalent interaction between BSA and CDMEAB, and such interactions were not observed in the absence of the salt. Protein structure remained nearly same in spite of strong interaction with CDMEAB as evident from the overall RMSD (root-mean-square deviation) values of the alpha carbons and backbone of the protein and RMSF (root-mean-square fluctuation) values of the amino acid residues present in BSA. In this work thermodynamic parameters of transfer (such as Δ G 0 m.tr. , Δ H 0 m.tr. , and Δ C 0 p.m.tr. ) were also evaluated and the results are discussed in detail. Besides, contributions of enthalpy and entropy to free energy changes were also analyzed., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Background: Sacroiliac joint dysfunction is a common cause of low back pain. Injection of autologous platelet rich fibrin (PRF) and platelet rich plasma (PRP) in the affected joint is a new option in this disorder management., Objective: To compare platelet concentrates (PRP and PRF) in injectable form in sacroiliac joint dysfunction., Methods: This is a non-randomized controlled trial between two groups (124 PRF patients and 62 PRP patients). All cases are treated by sacroiliac joint injection for sacroiliac joint pain., Results: Over 6 months of follow-up, there were statistically significant improvements in participants who received SIJ PRF injection with regards to pain measured by the Visual Analogue Scale (VAS), in comparison to PRP. In the two groups (PRF and PRP), there was significant difference in the post 2 VAS (6 months after the procedure) as the P value was 0.045. There was no significant difference in the pre VAS (P value of 0.909) and post 1 VAS (one month after the procedure) as the P value was 0.154. No adverse events of infection, neurologic injury, or any other complication were reported following the injection., Conclusions: Participants who received SIJ PRF experienced significant clinical improvement compared to those who received PRP in the late follow-up.

Objective: To investigate the image quality and x-ray dose associated with a transmission computed tomography (CT) component implemented within the same platform of an experimental benchtop x-ray fluorescence CT (XFCT) system for multimodal preclinical imaging applications., Methods: Cone-beam CT scans were performed using an experimental benchtop CT + XFCT system and a cylindrically-shaped 3D-printed polymethyl methacrylate phantom (3 cm in diameter, 7 cm in height) loaded with various concentrations (0.05-1 wt. %) of gold nanoparticles (GNPs). Two commercial CT quality assurance phantoms containing 3D line-pair (LP) targets and contrast targets were also scanned. The x-ray beams of 40 and 62 kVp, both filtered by 0.08 mm Cu and 0.4 mm Al, were used with 17 ms of exposure time per projection at three current settings (2.5, 5, and 10 mA). The ordered-subset simultaneous algebraic reconstruction and total variation-minimization methods were used to reconstruct images. Sparse projection and short scan were considered to reduce the x-ray dose. The contrast-to-noise ratio (CNR) and modulation transfer function (MTF) were calculated., Results: The lowest detectable concentration of GNPs (CNR > 5) and the highest spatial resolution (per MTF50%) were 0.10 wt. % and 9.5 LP/CM, respectively, based on the images reconstructed from 360 projections of the 40 kVp beam (or x-ray dose of 3.44 cGy). The background noise for the image resulting in the lowest GNP detection limit was 25 Hounsfield units., Conclusion: The transmission CT component within the current experimental benchtop CT + XFCT system produced images deemed acceptable for multimodal (CT + XFCT) imaging purposes, with less than 4 cGy of x-ray dose.

Large bone defects and bone loss after fractures remain significant challenges for orthopedic surgeons. Our study aims to find an available, applicable and biological treatment for bone regeneration overcoming the limitations in ESC/iPSC technology. We directly reprogrammed the mouse embryonic fibroblast (MEF) into osteoblast cells using different combinations of Yamanaka factors with human lim mineralization protein-3 (hLMP-3). LMP is an intracellular LIM-domain protein acting as an effective positive regulator of the osteoblast differentiation. After transduction, cells were cultured in osteogenic medium, and then examined for osteoblast formation. The expression of osteogenic markers (BMP2, Runx2 and Osterix) during reprogramming and in vitro mineralization assay revealed that the best reprogramming cocktail was (c-Myc - Oct4) with hLMP-3. In addition, both immunofluorescent staining and western blot analysis confirmed that osteocalcin (OCN) expression increased in the cells treated with the c-Myc/Oct4/hLMP3 cocktail than using hLMP-3 alone. Furthermore, this reprogramming cocktail showed efficient healing in an induced femoral bone defect in rat animal model one month after transplantation. In the present study, we reported for the first time the effect of combining Yamanaka factors with hLMP-3 to induce osteoblast cells from MEF both in vitro and in vivo., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: This work proposes a semiempirical correction method for attenuation of x-ray fluorescence (XRF) photons and/or an excitation beam during direct XRF imaging (i.e., mapping) of gold nanoparticle (GNP) distribution utilizing gold L-shell XRF photons., Methods: The current method was first devised by finding the two following relationships: (a) ratio of gold XRF peak intensity (L α at ~9.7 keV and L β at ~11.4 keV) vs pathlength of XRF photons; (b) XRF photon counts produced (N xrf ) vs scattered photon counts produced (N scat ). Monte Carlo simulations were performed using the Geant4 tool kit to characterize the aforementioned relationships for different tissue-like media. The applicability of the method was tested experimentally by acquiring 2D L-shell XRF images of custom-made phantoms using an experimental benchtop x-ray fluorescence computed tomography setup., Results: The results show that the ratio of gold L-shell XRF peak intensities allowed an estimation of the pathlength of XRF photons, thus can be utilized to correct for attenuation of XRF photons after emission. The results also demonstrate that N scat , through a proportionality N xrf ∝ N scat T where the exponent T depends on the energy of scattered photons, could be used to correct for attenuation of an excitation beam prior to producing XRF photons. The corrected XRF signal was found independent of the densities of tissue-like media present along the passage of an excitation beam or emitted XRF photons., Conclusions: The current results suggest that the developed attenuation correction method plays an essential role for the detection of GNPs on the order of parts-per-million, and also for the determination of GNP concentration/location within the imaging object made of tissue-like media, without any prior knowledge of the imaging object shape, under the conditions deemed relevant to biomedical applications of gold L-shell XRF-based imaging., (© 2018 American Association of Physicists in Medicine.)

This study established a single cloned chicken embryonic fibroblast (CEF) cell line. It solves the main problem of the instability of a cultured primary cell and its impact on the experiment. In this study, CEF pass through this crisis and formed a continuous cell line after subculture. We isolated single postcrisis CEF by a mouth pipette under a convert microscope then established a single cloned cell line named CSC-1-5 which passaged continuously from 96-well plates to 60 mm culture plates. CSC has a normal chicken diploid karyotype, no tumorigenicity, and a high G2/M phase cell ratio. We found that Fugene could mediate the transfection of CSCs efficiently; it was significantly improved compared with the primary cells. It could also promote the proliferation of chicken embryonic stem cell as a feeder layer., (© 2018 Wiley Periodicals, Inc.)

In this study, we developed and validated a Geant4-based Monte Carlo (MC) model of an experimental benchtop X-ray fluorescence (XRF) computed tomography (XFCT) system for quantitative imaging of metallic nanoparticles such as gold nanoparticles (GNPs) injected into small animals for preclinical testing of various NP-based diagnostic and therapeutic approaches. Detailed hardware components of the current benchtop XFCT system, including the X-ray source, excitation beam collimation and filtration, custom imaging phantoms with GNP solutions, and single/ring/linear array detectors with custom collimation, were incorporated into the MC model. In conjunction with a known CdTe detector response function, a deconvolution-based XRF signal extraction method was also developed in this study, which enabled complete separation of gold K-shell XRF peaks even when they almost overlapped and facilitated extraction of XRF signals from a broadband Compton scattered photon background. The extracted signal-to-background ratios were comparable with those expected using an ideal detector with high enough energy resolution (e.g., 0.1 keV full-width at half-maximum). Once convoluted with the CdTe detector response function, the MC-calculated spectra for excitation beams or emitted photons and XFCT image spatial resolutions agreed well with those measured experimentally. Thus, the current MC model can be used to optimize the beam/imaging parameters (e.g., beam geometry, excitation X-ray beam energy, and X-ray filter material) as well as the design of critical hardware components (e.g., detector collimators) within the current benchtop XFCT system. Also, the current XRF signal extraction method can relax the usual stringent requirement of detector energy resolution while not degrading the sensitivity of benchtop XFCT.

The presence of toxic polonium-210 (Po-210) in the environment is due to the decay of primordial uranium-238. Meanwhile, several studies have reported elevated Po-210 radioactivity in the rivers around the world due to both natural and anthropogenic factors. However, the primary source of Po-210 in Langat River, Malaysia might be the natural weathering of granite rock along with mining, agriculture and industrial activities. Hence, this is the first study to determine the Po-210 activity in the drinking water supply chain in the Langat River Basin to simultaneously predict the human health risks of Po-210 ingestion. Therefore, water samples were collected in 2015⁻2016 from the four stages of the water supply chain to analyze by Alpha Spectrometry. Determined Po-210 activity, along with the influence of environmental parameters such as time-series rainfall, flood incidents and water flow data (2005⁻2015), was well within the maximum limit for drinking water quality standard proposed by the Ministry of Health Malaysia and World Health Organization. Moreover, the annual effective dose of Po-210 ingestion via drinking water supply chain indicates an acceptable carcinogenic risk for the populations in the Langat Basin at 95% confidence level; however, the estimated annual effective dose at the basin is higher than in many countries. Although several studies assume the carcinogenic risk of Po-210 ingestion to humans for a long time even at low activity, however, there is no significant causal study which links Po-210 ingestion via drinking water and cancer risk of the human. Since the conventional coagulation method is unable to remove Po-210 entirely from the treated water, introducing a two-layer water filtration system at the basin can be useful to achieve SDG target 6.1 of achieving safe drinking water supplies well before 2030, which might also be significant for other countries.

For many years, tuberculosis (TB) has been endemic in Pakistan; many rare and unusual presentations have been reported. There is a myriad of non-specific symptoms which always requires a high index of clinical suspicion for TB. World Health Organization data suggest that Pakistan ranks as the fifth highest country burdened with TB and has the fourth highest prevalence of multi-drug resistant TB globally. With an annual incidence of 277 cases per 100,000, the importance of early diagnosis and treatment is self-evident. We present a case where a strong suspicion of isolated hepatosplenic TB in an immunocompetent patient justified a directed approach.

Auxetic scaffolds, that is, scaffolds that can display negative Poisson's ratio, have unique physical properties and can expand transversally when axially strained or contract under compression. Auxetic materials have been used for bioprostheses and artery stents due to the enhanced compressive strength and shear stiffness. In vascular tissue engineering, auxetic scaffolds allow the widening of blood vessels when blood flows through (creating compressive stress) to prevent the blockage. However, the influence of auxetic materials on the cellular fate decision in local environment is unclear. In this study, auxetic polyurethane foams were used to support vascular differentiation from pluripotent stem cells. The expression of alkaline phosphatase, Oct-4, and Nanog was lower after 4 days of differentiation for the cells grown in auxetic scaffolds. Higher expression of vascular markers CD31 and VE-cadherin was observed for the cells from auxetic scaffolds compared with those from the scaffolds before auxetic conversion. Little influence on the expression of cardiac marker α-actinin was observed. The vascular cells secreted extracellular matrix proteins vitronectin and laminin and expressed membrane-bound matrix metalloproteinase 9. The examination of Yes-associated protein expression indicated more cytoplasmic retention in the cells from auxetic scaffolds compared with those from regular scaffolds, suggesting that the auxetic scaffolds may affect cellular contraction. This study demonstrates a novel 3-D culture based on auxetic scaffolds for vascular differentiation and provides a platform to study the influence of biophysical microenvironments on differentiation of pluripotent stem cells. The outcome of this study has implications for regenerative medicine and drug discovery., (Copyright © 2018 John Wiley & Sons, Ltd.)

Background: Notch signaling is mainly regulated by Notch1 during development of chicken germ stem cells; however, the molecular mechanisms that contribute to generation of these germ stem cells have not been thoroughly investigated., Results: In our studies, Overexpression of the Notch1 NICD promoted development of the reproductive ridge, but inhibited the formation of seminiferous tubules. The formation efficiency of PGCs in the reproductive ridge following overexpression of NICD (7.5% ± 0.11) was significantly higher than that (4.9% ± 0.17, p  < 0.05) following inhibition of NICD, While the formation efficiency of spermatogonial stem cells (SSCs) in the testes (12.7% ± 0.08) was significantly lower after NICD overexpression than that after inhibition of NICD (16.3% ± 0.16, p  < 0.05). Using co-immunoprecipitation, we found that this anomaly stemmed from the reversal of dissociation of the Notch-regulated transcription factor CBF-1/RBP co-suppression complex during the differentiation of PGCs into SSCs. This dissociation of the CBF-1/RBP co-suppressing complex during the differentiation of ESCs into PGCs resulted in the release of HDAC1 and HDAC2 and the recruitment of mastermind-like 1 to form a coactive complex to promote the expression of the downstream transcription suppressor hairy/enhancer of split-1. Dynamic expression of transducin-like enhancer of split 3, TLE4, and C-terminal binding protein 2 during further differentiation of PGCs inhibited the dissociation of the CBF-1/RBP co-suppression complex and inhibited the expression of the downstream genes., Conclusions: In summary, Notch signaling plays diametrically opposing roles during normal development of chicken PGCs and SSCs, and these functions was determined by the expression of NICD, changes in the CBF-1/RBP complex composition, and histone modification.

Purpose: This study was performed to evaluate antifatigue effect of hydrogen water (HW) drinking in chronic forced exercise mice model., Materials and Methods: Twelve-week-old C57BL6 female mice were divided into nonstressed normal control (NC) group and stressed group: (purified water/PW-treated group and HW-treated group). Stressed groups were supplied with PW and HW, respectively, ad libitum and forced to swim for the stress induction every day for 4 consecutive weeks. Gross antifatigue effects of HW were assessed by swimming endurance capacity (once weekly for 4 wk), metabolic activities, and immune-redox activities. Metabolic activities such as blood glucose, lactate, glycogen, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) as well as immune-redox activities such as reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), catalase, and the related cytokines were evaluated to elucidate underlying mechanism. Blood glucose and lactate were measured at 0 wk (before swimming) and 4 wk (after swimming)., Results: HW group showed a higher swimming endurance capacity ( p < 0.001) than NC and PW groups. Positive metabolic effects in HW group were revealed by the significant reduction of blood glucose, lactate, and BUN in serum after 4 wk ( p < 0.01, resp.), as well as the significant increase of liver glycogen ( p < 0.001) and serum LDH ( p < 0.05) than PW group. In parallel, redox balance was represented by lower NO in serum ( p < 0.01) and increased level of GPx in both serum and liver ( p < 0.05) than PW group. In line, the decreased levels of serum TNF- α ( p < 0.01), IL-6, IL-17, and liver IL-1 β ( p < 0.05) in HW group revealed positive cytokine profile compared to PW and NC group., Conclusion: This study shows antifatigue effects of HW drinking in chronic forced swimming mice via metabolic coordination and immune-redox balance. In that context, drinking HW could be applied to the alternative and safety fluid remedy for chronic fatigue control.

Fibroblast growth factors (FGFs) are essential in regulating the formation of spermatogonial stem cells (SSCs). Here, we explored the effect of FGF8 on chicken SSCs formation by knockdown or overexpression of FGF8 in chicken embryonic stem cells (ESCs) both in vitro and in vivo. Our results showed that knockdown of FGF8 could facilitate the differentiation of ESCs into SSCs, overexpression of FGF8 could promote PGCs self-renewal, inhibit SSCs formation. This study further revealed the positive correlation between the expression level of FGF8 and MAPK/ERK signal. In the absence of FGF8, the expression of downstream genes such as FGFR2, GRB2, RAS, BRAF, RAF1, and MEK2 was not maintained, while overexpressing FGF8 enhances them. Thus, our study demonstrated that FGF8 can regulate germ cell fate by modulating the dynamic equilibrium between differentiation and self-renewal, which provides a new idea for the study of germ cell regulatory network., (© 2017 Wiley Periodicals, Inc.)

Steroid hormones regulate differentiation of various types of cell during embryogenesis. Testosterone is one of the androgens that bind to receptors to regulate gene expression and promote spermatogenesis. Our results showed that testosterone, as a product of steroid hormones synthesis pathway, could facilitate the differentiation of embryonic stem cells (ESCs) into spermatogonial stem cells (SSCs). The analysis of the steroid hormones synthesis pathway demonstrated that 3beta-hydroxysteroid dehydrogenase2 (Hsd3b2) plays a major role in the synthesis of testosterone. In the absence of Hsd3b2, the expression of downstream genes such as Cyp1a1, Ugt1a1, and Hsd17b7 was not maintained. This reduction is probably due to the down-regulation of the steroid hormones synthesis pathway. Furthermore, qRT-PCR, immunofluorescence, and flow cytometry analysis confirmed that the steroid hormones synthesis pathway could facilitate the differentiation of ESCs. Altogether, these results lead to a model in which Hsd3b2 regulates ESCs differentiation via modulating the activity of steroid hormones synthesis pathway., (© 2017 Wiley Periodicals, Inc.)

Theoretical investigations suggest that gold nanoparticle (GNP)-mediated radiation dose enhancement and radiosensitization can be maximized when photons interact with gold, predominantly via photoelectric absorption. This makes ytterbium (Yb)-169, which emits photons with an average energy of 93 keV (just above the K-edge of gold), an ideal radioisotope for such purposes. This investigation tests the feasibility of tumor-specific prostate brachytherapy achievable with Yb-169 and actively targeted GNPs, using an external beam surrogate of Yb-169 created from an exotic filter material - erbium (Er) and a standard copper-filtered 250 kVp beam. The current in vitro study shows that treatment of prostate cancer cells with goserelin-conjugated gold nanorods (gGNRs) promotes gonadotropin releasing hormone receptor-mediated internalization and enhances radiosensitivity to both Er-filtered and standard 250 kVp beams, 14 and 10%, respectively. While the degree of GNP-mediated radiosensitization as seen from the in vitro study may be considered moderate, the current in vivo study shows that gGNR treatment plus Er-filtered x-ray irradiation is considerably more effective than radiation treatment alone (p < 0.0005), resulting in a striking reduction in tumor volume (50% smaller) 2 months following treatment. Overall, the current results provide strong evidence for the feasibility of tumor-specific prostate brachytherapy with Yb-169 and gGNRs.

An array of homogeneous glycans representing all the major carbohydrate structures present in the cell wall of the human pathogen Mycobacterium tuberculosis and other mycobacteria has been probed with a panel of glycan-binding receptors expressed on cells of the mammalian innate immune system. The results provide an overview of interactions between mycobacterial glycans and receptors that mediate uptake and survival in macrophages, dendritic cells, and sinusoidal endothelial cells. A subset of the wide variety of glycan structures present on mycobacterial surfaces interact with cells of the innate immune system through the receptors tested. Endocytic receptors, including the mannose receptor, DC-SIGN, langerin, and DC-SIGNR (L-SIGN), interact predominantly with mannose-containing caps found on the mycobacterial polysaccharide lipoarabinomannan. Some of these receptors also interact with phosphatidyl-myo-inositol mannosides and mannose-containing phenolic glycolipids. Many glycans are ligands for overlapping sets of receptors, suggesting multiple, redundant routes by which mycobacteria can enter cells. Receptors with signaling capability interact with two distinct sets of mycobacterial glycans: targets for dectin-2 overlap with ligands for the mannose-binding endocytic receptors, while mincle binds exclusively to trehalose-containing structures such as trehalose dimycolate. None of the receptors surveyed bind furanose residues, which often form part of the epitopes recognized by antibodies to mycobacteria. Thus, the innate and adaptive immune systems can target different sets of mycobacterial glycans. This array, the first of its kind, represents an important new tool for probing, at a molecular level, biological roles of a broad range of mycobacterial glycans, a task that has not previously been possible.

Background: Cancer is one of the most dangerous diseases with quite a high mortality rate. Many quinazoline derivatives show potent anticancer activity., Objective: In this work our aim is to develop novel, safe and effective anticancer agents., Method: New 6,8-dibromo-2-(4-chlorophenyl)-quinazoline-sulphonamide hybrids and some Schiff´s base analogs were synthesized, and their structures were confirmed by spectral and elemental analysis. Cytotoxicity of all synthesized compounds was evaluated on three cancer cell lines MCF7, HCT116 and HEPG2 using sulpharodamine- B assay method and doxorubicin as a reference drug. All tested compounds show promising cytotoxic activities on the three cell lines., Results: Compound IXd was 2 times more active than doxorubicin on MCF7 cancer cells, while it was 3 times more potent than doxorubicin on HCT116 cancer cells. Compound IV was 2 times more active than doxorubicin while compound VI exhibited similar activity to doxorubicin on HEPG2 cell line. The most active compounds were tested against epidermal growth factor receptor tyrosine kinase (EGFR TK). Compounds IV, IXd, IXf show the most potent inhibitory percent 62.3, 91.1, 91.6 respectively. Compounds IV, V, VII, IXd, IXf caused a significant increase of CASP3 activity with range 86.5-37.6 %., Conclusion: The present work led to the discovery of new cytotoxic compounds having quinazoline pharmacophore., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Atopic dermatitis (AD) is a chronic relapsing allergic inflammatory skin disease that currently affects millions of children and adults worldwide. Drugs used to treat these inflammatory diseases include anti-histamines, corticosteroids and calcineurin inhibitors but these drugs have their limitations such as adverse effects with their long-term usage. Thus, researcher's interest in several alternative and complementary therapies are continually growing and balneotherapy is one of these approaches. Therefore, we investigate the bathing effect of high concentration mineral spring water (HMW) on redox balance and immune modulation in 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis like inflammation in hairless mice., Methods: We induced AD-like inflammation by application of DNCB on the dorsal skin of female skh-1 hairless mice. The mice were treated with 100% pure HMW (PHMW) and 10% diluted HMW (DHMW) through bathing once a day for 4 weeks. Tacrolimus ointment (0.1%) was used as positive control (PC) and only DNCB treatment as negative control (NeC) group. The severity of skin lesion inflammation was assessed through clinical scoring and observing scratching behavior. Levels of immunoglobulin E (IgE) and inflammatory cytokines in serum were detected by ELISA and multiplex bead array system, and the levels of oxidative stress-related biomarkers and antioxidant enzyme were also measured., Results: We found that HMW significantly decreased the scratching behavior in PHMW and DHMW groups at the 2nd week and in PHMW group at 4th week compared to NeC group. Likewise, serum IgE level was significantly decreased in DHMW group as compared to NeC group. In line, the level of inflammatory cytokines in serum such as interleukin (IL)-1β, IL-13 and tumor necrosis factor-α were significantly inhibited in PHMW and DHMW groups compared to NeC group. In parallel, total reactive oxygen species (ROS) of serum level was significantly decreased in PHMW treatment groups compared to NeC group. Consistently, serum malondialdehyde (MDA) level in PHMW group was lower than in NeC group. By contrast, glutathione peroxidase (GPx) activity was significantly enhanced in PHMW than NeC., Conclusion: Collectively, our study indicates a balneotherapeutic effect of HMW on DNCB-induced AD like inflammation in hairless mice via immunomodulation and redox balance.

Poly-ɛ-caprolactone (PCL) based microspheres have received much attention as drug or growth factor delivery carriers and tissue engineering scaffolds due to their biocompatibility, biodegradability, and tunable biophysical properties. In addition, PCL and polydimethylsiloxane (PDMS) can be fabricated into thermoresponsive shape memory polymers for various biomedical applications (e.g., smart sutures and vascular stents). However, the influence of biophysical properties of PCL-PDMS based microspheres on stem cell lineage commitment has not been well understood. In this study, PDMS was used as soft segments of varying length to tailor the elastic modulus of PCL-based copolymers. It was found that lower elastic modulus (<10 kPa) of the tri-block copolymer PCL-PDMS-PCL promoted vascular differentiation of embryonic stem cells, but the range of 60-100 MPa PCL-PDMS-PCL had little influence on cardiovascular differentiation. Then different sizes (30-140 μm) of PCL-PDMS-PCL microspheres were fabricated and incorporated with embryoid bodies (EBs). Differential expression of KDR, CD31, and VE-cadherin was observed for the EBs containing microspheres of different sizes. Higher expression of KDR was observed for the condition with small size of microspheres (32 μm), while higher CD31 and VE-cadherin expression was observed for the group of medium size of microspheres (94 μm). Little difference in cardiac marker α-actinin was observed for different microspheres. This study indicates that the biophysical properties of PCL-PDMS-PCL microspheres impact vascular lineage commitment and have implications for drug delivery and tissue engineering.

The study aims to analyze the key signaling pathways in regulating the process of embryonic stem cells (ESCs) differentiation into spermatogonial stem cells (SSCs). Based on RNA Sequencing result, we further explored the specific regulating mechanisms of Hedgehog (HH) signaling in this process. HH signaling was found to be a crucial signaling pathway participating in the differentiation process of ESCs to SSCs. In Retinoic acid (RA) induced in vitro differentiation assay, the expression of two germ cell marker genes, integrin α6, and integrin β1, was observed to significantly increase, while it decreased dramatically when IHH was knocked down. Fluorescence activated cell sorting analysis showed that the proportion of integrin α6 + and integrin β1 + cells in the RA group was significantly higher than that in the RA + siRNA- Indian Hedgehog (IHH) group. In in vivo situations, siRNA-IHH could stably express in fertilized chicken embryos and significantly down-regulate the IHH expression. With real-time quantitative PCR and western blot, we identified that integrin α6 and integrin β1 expression was significantly suppressed along with IHH inhibition in vivo. We concluded that Hedgehog signaling pathway positively regulates the differentiation of ESCs to male germ cells through signal transduction by IHH. J. Cell. Biochem. 118: 1379-1386, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Regulation of crucial lncRNAs involved in differentiation of chicken embryonic stem cells (ESCs) to spermatogonia stem cells (SSCs) was explored by sequencing the transcriptome of ESCs, primordial germ cells (PGCs) and SSCs with RNA-Seq; analytical bioinformatic methods were used to excavate candidate lncRNAs. We detected expression of candidate lncRNAs in ESCs, PGCs and SSCs and forecasted related target genes. Utilizing wego, david and string, function and protein-protein interactions of target genes were analyzed. Finally, based on string analysis, interaction diagrams and relevant signaling pathways were established. Our results indicate a total of 9657 lncRNAs in ESCs, PGCs and SSCs, with 3549 defined as significantly different. We screened 20 candidate lncRNAs, each demonstrating a greater than eight-fold difference in |logFC| value between groups (ESCs vs. PGCs, ESCs vs. SSCs and PGCs vs. SSCs) or specifically expressed in an individual cell type. qRT-PCR results indicated that expression tendencies of candidate lncRNAs were consistent with RNA-Seq. Fifteen cis and four trans target genes were forecasted. Based on wego and string analyses, we found lnc-SSC1, lnc-SSC5, lnc-SSC2 and lnc-ESC2 negatively regulated target genes SUFU, EPHA3, KLF3, ARL3 and TRIM8, whereas SHH, NOTCH, TGF-β, cAMP/cGMP and JAK/STAT signaling pathways were promoted, causing differentiation of ESCs into SSCs. Our findings represent a preliminary unveiling of lncRNA-associated regulatory mechanisms during differentiation of chicken ESCs into SSCs, filling a research void in male germ cell differentiation related to lncRNA. Our results also provide basic information for improving in vitro induction systems for differentiation of chicken ESCs into SSCs., (© 2016 Stichting International Foundation for Animal Genetics.)

Food and feed contamination by aflatoxin (AF)B₁ has adverse economic and health consequences. AFB₁ degradation by microorganisms or microbial enzymes provides a promising preventive measure. To this end, the present study tested 43 bacterial isolates collected from maize, rice, and soil samples for AFB₁-reducing activity. The higher activity was detected in isolate L7, which was identified as Bacillus shackletonii . L7 reduced AFB₁, AFB₂, and AFM₁ levels by 92.1%, 84.1%, and 90.4%, respectively, after 72 h at 37 °C. The L7 culture supernatant degraded more AFB₁ than viable cells and cell extracts; and the degradation activity was reduced from 77.9% to 15.3% in the presence of proteinase K and sodium dodecyl sulphate. A thermostable enzyme purified from the boiled supernatant was designated as Bacillus aflatoxin-degrading enzyme (BADE). An overall 9.55-fold purification of BADE with a recovery of 39.92% and an activity of 3.85 × 10³ U·mg -1 was obtained using chromatography on DEAE-Sepharose. BADE had an estimated molecular mass of 22 kDa and exhibited the highest activity at 70 °C and pH 8.0, which was enhanced by Cu 2+ and inhibited by Zn 2+ , Mn 2+ , Mg 2+ , and Li⁺. BADE is the major protein involved in AFB₁ detoxification. This is the first report of a BADE isolated from B. shackletonii , which has potential applications in the detoxification of aflatoxins during food and feed processing., Competing Interests: The authors declare no conflict of interest.

The tegument of herpesviruses is a highly complex structural layer between the nucleocapsid and the envelope of virions. Tegument proteins play both structural and regulatory functions during replication and spread, but the interactions and functions of many of these proteins are poorly understood. Here we focus on two tegument proteins from herpes simplex virus 1 (HSV-1), pUL7 and pUL51, which have homologues in all other herpesviruses. We have now identified that HSV-1 pUL7 and pUL51 form a stable and direct protein-protein interaction, their expression levels rely on the presence of each other, and they function as a complex in infected cells. We demonstrate that expression of the pUL7-pUL51 complex is important for efficient HSV-1 assembly and plaque formation. Furthermore, we also discovered that the pUL7-pUL51 complex localizes to focal adhesions at the plasma membrane in both infected cells and in the absence of other viral proteins. The expression of pUL7-pUL51 is important to stabilize focal adhesions and maintain cell morphology in infected cells and cells infected with viruses lacking pUL7 and/or pUL51 round up more rapidly than cells infected with wild-type HSV-1. Our data suggest that, in addition to the previously reported functions in virus assembly and spread for pUL51, the pUL7-pUL51 complex is important for maintaining the attachment of infected cells to their surroundings through modulating the activity of focal adhesion complexes., Importance: Herpesviridae is a large family of highly successful human and animal pathogens. Virions of these viruses are composed of many different proteins, most of which are contained within the tegument, a complex structural layer between the nucleocapsid and the envelope within virus particles. Tegument proteins have important roles in assembling virus particles as well as modifying host cells to promote virus replication and spread. However, little is known about the function of many tegument proteins during virus replication. Our study focuses on two tegument proteins from herpes simplex virus 1 that are conserved in all herpesviruses: pUL7 and pUL51. We demonstrate that these proteins directly interact and form a functional complex that is important for both virus assembly and modulation of host cell morphology. Further, we identify for the first time that these conserved herpesvirus tegument proteins localize to focal adhesions in addition to cytoplasmic juxtanuclear membranes within infected cells., (Copyright © 2017 Albecka et al.)

Background: Cancer is a major health problem to human beings around the world. Many quinazoline derivatives were reported to have potent cytotoxic activity., Aims: Our aim in this work is the discovery of potent epidermal growth factor receptor (EGFR) inhibitors with anti-breast cancer activity containing 4-substituted quinazoline pharmacophore., Method: Novel series of 4-substituted 6,8-dibromo-2-(4-chlorophenyl)-quinazoline derivatives have been designed and synthesized. New derivatives were tested against MCF-7 (human breast carcinoma cell line) and screened for their inhibition activity against epidermal growth factor receptor tyrosine kinase (EGFR-TK)., Result: Most of the tested compounds show potent antiproliferative activity and EGFR-TK inhibitory activity. Compounds VIIIc and VIIIb exerted powerful cytotoxic activity (IC50 3.1 and 6.3 μM) with potent inhibitory percent (91.1 and 88.4%) against EGFR-TK. Compounds IX, VIIa, X, VIIb, VIc, V, IV, VIa and VIb showed promising cytotoxic effects with IC50 range (12-79 μM) with good activity against EGFR-TK with the inhibitory percent (85.4-60.8%). On the other hand, compounds VIIc, VIIIa exerted low cytotoxic effects as revealed from their IC50 value (124 and 144 μM) with low activity against EGFR-TK with inhibitory percent 30.6 and 29.1% respectively., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: To investigate the efficacy of intralipid supplementation in women with recurrent spontaneous abortion (RSA) and elevated natural killer cell activity undergoing in vitro fertilization/intracytoplasmic sperm injection., Methods: Between February 10, 2013, and April 30, 2015, a double-blind randomized controlled study was conducted at a center in Egypt. Women with unexplained secondary infertility, RSA, and elevated levels of natural killer cells (>12%) were enrolled and randomly assigned to receive intralipid (2mL diluted at 20% in 250mL saline) or saline (250mL) infusion on the day of oocyte retrieval using random numbers and sealed envelopes. Patients and attending physicians were masked to group assignment. The infusions were repeated within 1week of a positive pregnancy test and then every 2weeks until the end of the first trimester. The primary outcome was chemical pregnancy 14days after embryo transfer. Analyses were by intention-to-treat., Results: Overall, 296 women were enrolled. Chemical pregnancy was recorded for 84 (58.3%) of 144 women in the intralipid group and 76 (50.0%) of 152 in the control group (P=0.129)., Conclusion: Intralipid supplementation did not increase frequency of chemical pregnancy. However, findings related to ongoing pregnancy and live birth should be investigated further. ClinicalTrials.gov:NCT01788540., (Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Introduction: The use of corticosteroids or antihistaminics in treatment of allergic rhinitis is known and practiced since long. The efficacy of topical use of fluticasone propionate and Olopatadine Hydrochloride (HCL) for symptomatic relief of allergic rhinitis has been studied either individually or with other drugs. But very few studies show comparison between these two drugs., Aim: To compare the efficacy of topical use of fluticasone propionate and olopatadine hydrochloride for symptomatic relief of allergic rhinitis., Design: In this single blind, randomized control study, the efficacy of topical use of olopatadine HCL was compared with fluticasone propionate for relieving symptoms of allergic rhinitis., Materials and Methods: The symptomatic cases were randomized in two groups for treatment using either olopatadine HCL or fluticasone propionate respectively. In each group, the Total Symptom Scores (TSS) and individual symptom scores were recorded before and after treatment with the help of symptom evaluation scale., Statistical Analysis: Chi-square test, unpaired t-test, Mann Witney U-test, and Wilcoxon signed Rank test were used during analysis. The results of the comparison were noted and analysed., Results: During four week study period both TSS and individual symptom score were reduced (p<0.05) in either groups. The TSS decreased by an average of 85.07% for those treated with olopatadine and by 95.55% for those treated with fluticasone., Conclusion: Overall fluticasone propionate was superior to olopatadine in relieving symptoms of allergic rhinitis (p<0.005).

This work evaluates the dosimetric properties of newly developed optically stimulated luminescence (OSL) films, fabricated with either Al 2 O 3 :C or Al 2 O 3 :C,Mg, using a prototype laser scanning reader, a developed image reconstruction algorithm, and a 6 MV therapeutic photon beam. Packages containing OSL films (Al 2 O 3 :C and Al 2 O 3 :C,Mg) and a radiochromic film (Gafchromic EBT3) were irradiated using a 6 MV photon beam using different doses, field sizes, with and without wedge filter. Dependence on film orientation of the OSL system was also tested. Diode-array (MapCHECK) and ionization chamber measurements were performed for comparison. The OSLD film doses agreed with the MapCHECK and ionization chamber data within the experimental uncertainties (<2% at 1.5 Gy). The system background and minimum detectable dose (MDD) were  <0.5 mGy, and the dose response was approximately linear from the MDD up to a few grays (the linearity correction was  <10% up to ~2-4 Gy), with no saturation up to 30 Gy. The dose profiles agreed with those obtained using EBT3 films (analyzed using the triple channel method) in the high dose regions of the images. In the low dose regions, the dose profiles from the OSLD films were more reproducible than those from the EBT3 films. We also demonstrated that the OSL film data are independent on scan orientation and field size over the investigated range. The results demonstrate the potential of OSLD films for 2D dosimetry, particularly for the characterization of small fields, due to their wide dynamic range, linear response, resolution and dosimetric properties. The negligible background and potential simple calibration make these OSLD films suitable for remote audits. The characterization presented here may motivate further commercial development of a 2D dosimetry system based on the OSL from Al 2 O 3 :C or Al 2 O 3 :C,Mg.

A dual-channel streaked soft x-ray imager has been designed and used on high energy-density physics experiments at the National Ignition Facility. This streaked imager creates two images of the same x-ray source using two slit apertures and a single shallow angle reflection from a nickel mirror. Thin filters are used to create narrow band pass images at 510 eV and 360 eV. When measuring a Planckian spectrum, the brightness ratio of the two images can be translated into a color-temperature, provided that the spectral sensitivity of the two images is well known. To reduce uncertainty and remove spectral features in the streak camera photocathode from this photon energy range, a thin 100 nm CsI on 50 nm Al streak camera photocathode was implemented. Provided that the spectral shape is well-known, then uncertainties on the spectral sensitivity limits the accuracy of the temperature measurement to approximately 4.5% at 100 eV.

Recent experiments at the Sandia National Laboratory Z facility have called into question models used in calculating opacity, of importance for modeling stellar interiors. An effort is being made to reproduce these results at the National Ignition Facility (NIF). These experiments require a new X-ray opacity spectrometer (OpSpec) spanning 540 eV-2100 eV with a resolving power E/ΔE > 700. The design of the OpSpec is presented. Photometric calculations based on expected opacity data are also presented. First use on NIF is expected in September 2016.

The objective of this work was to develop an image reconstruction algorithm for 2D dosimetry using Al 2 O 3 :C and Al 2 O 3 :C,Mg optically stimulated luminescence (OSL) films imaged using a laser scanning system. The algorithm takes into account parameters associated with detector properties and the readout system. Pieces of Al 2 O 3 :C films (~8 mm  ×  8 mm  ×  125 µm) were irradiated and used to simulate dose distributions with extreme dose gradients (zero and non-zero dose regions). The OSLD film pieces were scanned using a custom-built laser-scanning OSL reader and the data obtained were used to develop and demonstrate a dose reconstruction algorithm. The algorithm includes corrections for: (a) galvo hysteresis, (b) photomultiplier tube (PMT) linearity, (c) phosphorescence, (d) 'pixel bleeding' caused by the 35 ms luminescence lifetime of F-centers in Al 2 O 3 , (e) geometrical distortion inherent to Galvo scanning system, and (f) position dependence of the light collection efficiency. The algorithm was also applied to 6.0 cm  ×  6.0 cm  ×  125 μm or 10.0 cm  ×  10.0 cm  ×  125 µm Al 2 O 3 :C and Al 2 O 3 :C,Mg films exposed to megavoltage x-rays (6 MV) and 12 C beams (430 MeV u -1 ). The results obtained using pieces of irradiated films show the ability of the image reconstruction algorithm to correct for pixel bleeding even in the presence of extremely sharp dose gradients. Corrections for geometric distortion and position dependence of light collection efficiency were shown to minimize characteristic limitations of this system design. We also exemplify the application of the algorithm to more clinically relevant 6 MV x-ray beam and a 12 C pencil beam, demonstrating the potential for small field dosimetry. The image reconstruction algorithm described here provides the foundation for laser-scanned OSL applied to 2D dosimetry.

Introduction: Industrial livestock farming is a possible source of multi-resistant Gram-negative bacteria, including producers of extended spectrum beta-lactamases (ESBLs) conferring resistance to 3rd generation cephalosporins. Limited information is currently available on the situation of ESBL producers in livestock farming outside of Western Europe. A surveillance study was conducted from January to May in 2014 in four dairy cattle farms in different areas of the Nile delta, Egypt., Materials and Methods: In total, 266 samples were collected from 4 dairy farms including rectal swabs from clinically healthy cattle (n = 210), and environmental samples from the stalls (n = 56). After 24 h pre-enrichment in buffered peptone water, all samples were screened for 3rd generation cephalosporin-resistant Escherichia coli using Brilliance™ ESBL agar. Suspected colonies of putatively ESBL-producing E. coli were sub-cultured and subsequently genotypically and phenotypically characterized. Susceptibility testing using the VITEK-2 system was performed. All suspect isolates were genotypically analyzed using two DNA-microarray based assays: CarbDetect AS-1 and E. coli PanType AS-2 kit (ALERE). These tests allow detection of a multitude of genes and their alleles associated with resistance toward carbapenems, cephalosporins, and other frequently used antibiotics. Serotypes were determined using the E. coli SeroGenotyping AS-1 kit (ALERE)., Results: Out of 266 samples tested, 114 (42.8%) ESBL-producing E. coli were geno- and phenotypically identified. 113 of 114 phenotypically 3rd generation cephalosporin-resistant isolates harbored at least one of the ESBL resistance genes covered by the applied assays [blaCTX-M15 (n = 105), blaCTX-M9 (n = 1), blaTEM (n = 90), blaSHV (n = 1)]. Alarmingly, the carbapenemase genes blaOXA-48 (n = 5) and blaOXA-181 (n = 1) were found in isolates that also were phenotypically resistant to imipenem and meropenem. Using the array-based serogenotyping method, 66 of the 118 isolates (55%) could be genotypically assigned to O-types., Conclusion: This study is considered to be a first report of the high prevalence of ESBL-producing E. coli in dairy farms in Egypt. ESBL-producing E. coli isolates with different underlying resistance mechanisms are common in investigated dairy cattle farms in Egypt. The global rise of ESBL- and carbapenemase-producing Gram-negative bacteria is a big concern, and demands intensified surveillance.

Background: The need for organic food of animal origin has increased rapidly in recent years. However, effects of organic animal husbandry on food safety have not been rigorously tested especially in meat turkey flocks. This study provides for the first time an overview on the prevalence and genetic diversity of Campylobacter species (spp.) in five organic meat turkey farms located in different regions in Germany, as well as on potential risk factors of bacterial spreading. Thirty cloacal swabs as well as water samples and darkling beetles were collected from each flock and examined for the presence of Campylobacter by conventional and molecular biological methods. The isolates were genotyped by flaA-RFLP., Results: Campylobacter spp. were detected in cloacal swabs in all 5 turkey flocks with prevalence ranged from 90.0 to 100 %. 13 cloacal swabs collected from birds in farm III and IV were harboured mixed population of thermophilic campylobacters. In total, from 158 Campylobacter isolated from turkeys 89 (56.33 %) were identified as C. coli and 69 (43.76 %) as C. jejuni. Three Campylobacter (2 C. jejuni and 1 C. coli) were detected in drinkers of two farms and 3 C. coli were isolated from darkling beetles of one farm. No Campylobacter were isolated from main water tanks. flaA-RFLP assay showed that turkey farms can harbour more than one genotype. In a single turkey two different genotypes could be detected. The genotypes of campylobacters isolated from water samples or beetles were identical with those isolated from turkeys. No effect was found of some environmental parameters [ammonia concentration (NH3), carbon dioxide concentration (CO2), relative humidity (RH) and air temperature)] on Campylobacter prevalence in organic turkey farms. Additionally, drinking water and darkling beetles might be considered as risk factors for the spreading of Campylobacter in turkey flocks., Conclusions: This study highlights the high prevalence and genotypic diversity of Campylobacter spp. isolated from organic turkey flocks. Further research is needed to assess other potential risk factors responsible for bacteria spreading in order to mitigate the spread of Campylobacter in organic turkey flocks by improving biosecurity control measures.

Background: Influenza viruses may cause severe acute respiratory illness among human population. People of densely populated areas, e.g., slum, are mostly affected by influenza viruses. Although potential vaccines to influenza viruses have been developed, infection rate is still high, therefore, increase the morbidity and mortality rate in slum areas. To treat these infections, slum dwellers including children and mothers do not get proper medication as well as vaccination. Hence, prevention remains to be the only mean to tackle such infections. Herein, we determined the prevalence of influenza infections among nutritionally deprived children and mothers of slum areas in Dhaka city and demonstrated the association with different risk factors like age, gender and socio-economic status., Results: Nasopharyngeal swab samples and a short demography of all the participants suffering from influenza-like illness (ILI) were collected. The samples were subjected to RNA extraction and then real-time RT-PCR to detect influenza viruses. Among the ILI patients, about 87.9 % did not have knowledge about influenza infections and 80.5 % did not cover their noses during coughing as well as sneezing. Children were significantly infected by both influenza A and influenza B viruses, suggesting their vulnerability to these infections. Additionally, among the children with ILI, influenza infections were significantly associated with age below or equal to three years, very poor family incomes, practicing unhygienic habits and nutritional deficiency., Conclusions: This study suggests that proper vaccination, improved sanitary conditions and nutritional diet may help reduce the risk of influenza infections in slum areas.

This study compared the influence of type 2 diabetes on the occurrence of six periodontal pathogens in plaque samples of patients with and without chronic periodontitis. Levels of salivary MMP-8, MMP-9, RANKL, and OPG were also investigated. The study enrolled 31 patients with type 2 diabetes and chronic periodontitis (DM + CP), 29 with chronic periodontitis (CP), and 20 with type 2 diabetes (DM). Questionnaire-guided interviews were conducted and plaque index, bleeding on probing, and pocket depth were recorded. Polymerase chain reaction (PCR) was utilized to determine the prevalence of the bacteria. The levels of salivary molecules were determined by enzyme immunosorbent assay (ELISA). The CP group had the highest prevalence of P. gingivalis (81.5%), followed by the DM + CP (59.3%) and DM (55.0%) groups (P > 0.05). Similar trends were observed for P. intermedia and T. denticola. The prevalence of T. forsythia was 100% in both periodontitis groups compared to 90% in the DM group. There were no significant differences between the groups regarding the concentrations of MMP-8, MMP-9, or OPG. RANKL concentrations were below the detection limit. Our data show that type 2 diabetes has no significant influence on the prevalence of the investigated periodontal pathogens, or the levels of salivary MMP-8, MMP-9, and OPG.

Scalp masses are commonly seen in clinical practice. They range from simple sebaceous cyst to malignant neoplasms. Clinical presentation is straight forward in most of the cases. Simple subcutaneous swelling till erosion of scalp and skull all can occur. However very few intracranial masses present with exophytic scalp swelling. This is because they have to erode dura, thick skull bone and all the layers of scalp to appear out on scalp. It is very unusual that an intracranial mass present like a scalp swelling. Some of the intracranial masses have tendency to erode skull. Dermoid & meningioma are among the most common.

A new series of 6,8-dibromo-2-(4-chlorophenyl)-4-oxo-4H-quinazoline derivatives II-VI were syn- thesized, their chemical structures were confirmed by spectroscopic means and elemental analyses. All these compounds were tested in vitro against human breast cancer cell line (MCF-7) using resazurin reduction assay method and doxorubicin as a reference drug. Most of the tested compounds showed better activity than dox- orubicin. Compound IVh was the best active one, its IC₅₀ is 8.52 µg/mL. Molecular docking studies for the best active compounds IVb, IVc, IVf, IVh and Va were performed on the active site of estrogen receptor α (ERα) subtype to explore the estrogen receptor binding ability of these compounds. All the docked compounds showed good fitting score energy with the active site of ERα subtype and compound IVh showed the best docking score energy(-25.3 kcal/mol). Estrogen binding evaluation assay was performed for the docked compounds to ensure that their activity against MCF7 go through inhibition of ERα, they showed ERα inhibition at 41-85% and compound IVh was the most active one (85%).

This paper describes and investigates the performance of an algorithm to correct for "pixel bleeding" caused by slow luminescence centers in laser scanning imaging (e.g., X-ray imaging using photostimulable phosphors and 2D dosimetry using optically stimulated luminescence). The algorithm is based on a deconvolution procedure that takes into account the lifetime of the slow luminescence center and is further constrained by the detection of fast and slow luminescence centers and combining rows scanned in opposite directions. The algorithm was tested using simulated data and demonstrated experimentally by applying it to image reconstruction of two types of Al2O3 X-ray detector films ( Al2O3:C and Al2O3 :C,Mg), whose use in 2D dosimetry in conjunction with laser-scanning readout has so far been prevented by slow luminescence centers (F-centers, 35 ms lifetime). We show that the algorithm allows the readout of Al2O3 film detectors 300-500 times faster than generally allowed considering the lifetime of the main luminescence centers. By relaxing the stringent requirements on the detector's luminescence lifetime, the algorithm opens the possibility of using new materials in 2D dosimetry as well as other laser scanning applications, such as X-ray imaging using storage phosphors and scanning confocal microscopy, although the effect of the noise introduced must be investigated for each specific application.

The popularity of food produced from animals kept under an organic regimen has increased in recent years. In Germany, turkey meat consumption has increased. Despite several studies assessing the susceptibility of campylobacters to various antibiotics in poultry, no sufficient data exists regarding the antimicrobial resistance of campylobacters in organic-reared turkeys. This study provides information about antibiotic resistance in Campylobacter isolated from turkeys reared on organic farms in Germany. Ninety-six Campylobacter strains (41 C. jejuni and 55 C. coli) were isolated from different free-range turkey flocks. In vitro antimicrobial sensitivity testing was done using a broth microdilution test, and the presence of resistance genes to antibiotics (ciprofloxacin, tetracycline) was investigated. All Campylobacter isolates from organic turkeys (n = 96) were phenotypically sensitive to gentamicin, erythromycin, streptomycin, and chloramphenicol. In this study, the antibiotic susceptibilities of C. jejuni to ciprofloxacin, tetracycline, and naladixic acid were 56.0%, 51.3%, and 56.0%, respectively. In contrast, 44.0%, 73.0%, and 74.6% of C. coli isolates were resistant to tetracycline, ciprofloxacin, and nalidixic acid, respectively. Replacement of the Thr-86→Ile in the gyrA gene, and the presence of the tet(O) gene were the mainly identified resistance mechanisms against fluoroquinolones and tetracycline, respectively.These results also reinforce the need to develop strategies and implement specific control procedures to reduce the development of antimicrobial resistance., (© 2015 Poultry Science Association Inc.)

Our study aimed to explore the regulatory mechanism of the carbohydrate metabolism signaling pathways and related genes during the differentiation of chicken embryonic stem cells to male germ cells, providing the basis for improving the efficiency of the in vitro induction system. Cell sorting was used to obtain highly purified embryonic stem cells (ESCs), primitive germ cells (PGCs), and spermatogonial stem cells (SSCs). The total RNA was then extracted from each cell type. The transcriptions of ESCs, PGCs, and SSCs were sequenced by DNA microarray and mRNA sequencing (RNA-seq). The results were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. The key pathways and genes of carbohydrate metabolism were screened during the differentiation process of chicken male germ cell. We concluded that 419 differentially expressed genes enriched to 26 carbohydrate metabolism pathways during the differentiation process of ESCs to SSCs, all of the chondroitin sulfate (CS) signaling pathway was significant. We screened the key genes CHSY3, B3GAT1, CHPF, and B4GALT7 which was significantly expressed in CS pathway. Quantitative RT-PCR showed that the expression trend of these genes is consistent with DNA Microarray and RNA-seq results. Our study supports the opinion that CS pathway is significantly different during the differentiation of chicken male germ cell (P < 0.05) and that CHSY3, B3GAT1, CHPF, and B4GALT7 are key genes.

We explored the regulatory mechanism of protein metabolism during the differentiation process of chicken male germ cells and provide a basis for improving the induction system of embryonic stem cell differentiation to male germ cells in vitro. We sequenced the transcriptome of embryonic stem cells, primordial germ cells, and spermatogonial stem cells with RNA sequencing (RNA-Seq), bioinformatics analysis methods, and detection of the key genes by quantitative reverse transcription PCR (qRT-PCR). Finally, we found 16 amino acid metabolic pathways enriched in the biological metabolism during the differentiation process of embryonic stem cells to primordial germ cells and 15 amino acid metabolic pathways enriched in the differentiation stage of primordial germ cells to spermatogonial stem cells. We found three pathways, arginine-proline metabolic pathway, tyrosine metabolic pathway, and tryptophan metabolic pathway, significantly enriched in the whole differentiation process of embryonic stem cells to spermatogonial stem cells. Moreover, for these three pathways, we screened key genes such as NOS2, ADC, FAH, and IDO. qRT-PCR results showed that the expression trend of these genes were the same to RNA-Seq. Our findings showed that the three pathways and these key genes play an important role in the differentiation process of embryonic stem cells to male germ cells. These results provide basic information for improving the induction system of embryonic stem cell differentiation to male germ cells in vitro.

Background: Pathological changes in periodontal tissues are mediated by the interaction between microorganisms and the host immune-inflammatory response. Hyperglycemia may interfere with this process. The aim of this study was to compare the levels of 27 inflammatory molecules in the gingival crevicular fluid (GCF) of patients with type 2 diabetes, with and without chronic periodontitis, and of chronic periodontitis subjects without diabetes. A putative correlation between glycated haemoglobin (HbA1c) and levels of the inflammatory molecules was also investigated., Methods: The study population comprised a total of 108 individuals, stratified into: 54 with type 2 diabetes and chronic periodontitis (DM + CP), 30 with chronic periodontitis (CP) and 24 with type 2 diabetes (DM). Participants were interviewed with the aid of structured questionnaire. Periodontal parameters (dental plaque, bleeding on probing and periodontal pocket depth) were recorded. The GCF levels of the 27 inflammatory molecules were measured using multiplex micro-bead immunoassay. A glycated haemoglobin (HbA1c) test was performed for patients with diabetes by boronate affinity chromatography., Results: After adjustment for potential confounders, the DM + CP group had higher levels of IL-8 and MIP-1β, and lower levels of TNF-α, IL-4, INF-γ, RANTES and IL-7 compared to the CP group. Moreover, the DM + CP group had lower levels of IL-6, IL-7 and G-CSF compared to the DM group. The DM group had higher levels of IL-10, VEGF, and G-CSF compared to the CP group. The levels of MIP-1α and FGF were lower in diabetes patients (regardless of their periodontal status) than in chronic periodontitis subjects without diabetes. Diabetes patients (DM + CP and DM) had higher Th-2/Th-1 ratio compared to the CP group. HbA1c correlated positively with the pro-inflammatory cytokines (Pearson correlation coefficient = 0.27, P value: 0.02)., Conclusion: Type 2 diabetes and chronic periodontitis may influence the GCF levels of inflammatory molecules synergistically as well as independently. Type 2 diabetes was associated with high Th-2/Th-1 ratio, and modulated the local expression of molecules involved in the anti-inflammatory and healing processes.